The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
Free fatty acids promote hepatic lipotoxicity by stimulating TNF-α expression via a lysosomal pathway
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a serious health problem. Although NAFLD represents a form of lipotoxicity, its pathogenesis remains poorly understood. The aim of this study was to examine the cellular mechanisms involved in free fatty acid (FFA)-mediated hepatic lipotoxicity. FFA treatment of liver cells resulted in Bax translocation to lysosomes and lysosomal destabilization with release of cathepsin B (ctsb), a lysosomal cysteine protease, into the cytosol. This process was also partially dependent on ctsb. Lysosomal destabilization resulted in nuclear factor κB-dependent tumor necrosis factor α expression. Release of ctsb into the cytoplasm was also observed in humans with NAFLD and correlated with disease severity. In a dietary murine model of NAFLD, either genetic or pharmacological inactivation of ctsb protected against development of hepatic steatosis, liver injury, and insulin resistance with its associated “dysmetabolic syndrome.” In conclusion, these data support a lipotoxic model of FFA-mediated lysosomal destabilization. Supplemental material for this article can be found on the Hepatology website (http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index.html). (Hepatology 2004;40:185-194.)
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Cites
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Nonalcoholic Fatty Liver Disease
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Cited by
Evolution of inflammation in nonalcoholic fatty liver disease: The multiple parallel hits hypothesis
Tilg, H., & Moschen, A. R. (2010) · Hepatology · doi:10.1002/hep.24001 · Cited by 2,548
A lipidomic analysis of nonalcoholic fatty liver disease
Puri, P., Baillie, R. A., Wiest, M. M., Mirshahi, F., Choudhury, J., Cheung, O., Sargeant, C., Contos, M. J., & Sanyal, A. J. (2007) · Hepatology · doi:10.1002/hep.21763 · Cited by 1,338
Neuschwander‐Tetri, B. A. (2010) · Hepatology · doi:10.1002/hep.23719 · Cited by 1,077
Triggering and resolution of inflammation in NASH
Schuster, S., Cabrera, D., Arrese, M., & Feldstein, A. E. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-018-0009-6 · Cited by 943
Self-citationNonalcoholic Fatty Liver Disease: Pathology and Pathogenesis
Tiniakos, D. G., Vos, M. B., & Brunt, E. M. (2010) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-121808-102132 · Cited by 870
Metadata
- Authors
- Feldstein, A. E., Werneburg, N. W., Canbay, A., Guicciardi, M. E., Bronk, S. F., Rydzewski, R., Burgart, L. J., & Gores, G. J.
- Venue
- Hepatology
- Published
- 2004-07
- Volume
- 40
- Issue
- 1
- Pages
- 185-194
- ISSN
- 0270-9139 (ISSN-L)
- OpenAlex
- W1984077928
- Cited by
- 834
- References
- 11
- FWCI
- 18.23
- Type
- journal article
- Language
- en
- Open access
- closed
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